PurposeThe aquaporin (AQP) family consists of a number of small integral membrane proteins that transport water and glycerol. AQPs are critical for trans-epithelial fluid transport. Recent reports demonstrated that AQPs, particularly AQP1 and AQP5, are expressed in high grade tumor cells of a variety of tissue origins, and that AQPs are involved in cell migration and metastasis. Based on this background, we examined whether AQP3, another important member of the AQP family, could facilitate cell migration in human breast cancers.MethodsPotential role of AQP3 was examined using two representative breast cancer cell lines (MDA-MB-231 and Bcap-37). Briefly, AQP3 expression was inhibited with a lentivirus construct that stably expressed shRNA against the AQP3 mRNA. AQP3 expression inhibition was verified with Western blot. Cell migration was examined using a wound scratch assay in the presence of fibroblast growth factor-2 (FGF-2). In additional experiments, AQP3 was inhibited by CuSO4. Fibroblast growth factor receptor (FGFR) kinase inhibitor PD173074, PI3K inhibitor LY294002, and MEK1/2 inhibitor PD98059 were used to dissect the molecular mechanism of FGF-2 induced AQP3 expression.ResultsFGF-2 treatment increased AQP3 expression and induced cell migration in a dose dependent manner. Silencing AQP3 expression by a lentiviral shRNA inhibited FGF-2 induced cell migration. CuSO4, a water transport inhibitor selective for AQP3, also suppressed FGF-2-induced cell migration. The FGFR kinase inhibitor PD173074, significantly inhibited FGF-2-induced AQP3 expression and cell migration. The PI3K inhibitor LY294002 and MEK1/2 inhibitor PD98059 inhibited, but not fully blocked, FGF-2-induced AQP3 expression and cell migration.ConclusionsAQP3 is required for FGF-2-induced cell migration in cultured human breast cancer cells. Our findings also suggest the importance of FGFR-PI3K and FGFR-ERK signaling in FGF-2-induced AQP3 expression. In summary, our findings suggest a novel function of AQP3 in cell migration and metastasis of breast cancers.
Many studies have reported that selenium (Se) has a close relationship with autoimmune thyroiditis (AIT). The therapeutic effect of Se supplementation in AIT treatment remains unclear. The objective of the present study was to determine the efficacy of Se supplementation for the treatment of AIT. A structured literature search was undertaken to identify all randomized controlled trials conducted in patients with AIT receiving Se supplementation or placebo. Nine studies enrolling a total of 787 patients were included. The results showed that Se supplementation with duration 6 months significantly dropped the TPOAb titers but did not decrease the TgAb titers. Patients assigned to Se supplementation for 12-month duration showed significantly lower TPOAb titers and TgAb titers. Patients after Se supplementation had a higher chance to improve the mood or well-being compared with controls. Se supplementation is associated with a significant decrease in TPOAb titers at 6 and 12 months; meanwhile, the TgAb titers can be dropped at 12 months. After Se supplementation treatment, patients had a higher chance to improve the mood without significant adverse events.
Objective The objective was to assess the association between 25-hydroxyvitamin D (25OHD) level and diabetic kidney disease (DKD) in Chinese patients with type 2 diabetes. Methods Data pertaining to 351 in-patients with type 2 diabetes were collected. Subjects were classified into three groups based on the level of urinary albumin-to-creatinine ratio (UACR). UACR < 30 mg/g was defined as normoalbuminuria, while UACR levels of 30–300 mg/g and ≥ 300 mg/g were defined as microalbuminuria and macroalbuminuria, respectively. Serum 25OHD and other clinical characteristics among various UACR groups were compared. The relationship between albuminuiria and 25OHD was analyzed. Results The prevalence of 25OHD insufficiency in the microalbuminuria group was significantly higher than that in the normoalbuminuria group (25.1% vs . 19.6%; P < 0.05); patients with macroalbuminuria had the highest prevalence of 25OHD deficiency (37.8%; P < 0.01 versus normoalbuminuria). Logistic regression analyses demonstrated that low 25OHD levels were associated with DKD [odds ratio ( OR) = 1.51, 95% confidence interval ( CI ) 1.16–1.97). The association was more robust after adjusting for sex, hypertension, increased systolic blood pressure, glycemic status, and hyperuricemia ( OR = 1.62, 95% CI 1.19–2.20). Conclusions The prevalence of vitamin D insufficiency/deficiency in patients with albuminuria was overtly higher than that in patients without albuminuria among Chinese adults with type 2 diabetes. Vitamin D insufficiency/deficiency was independently associated with DKD in type 2 diabetes.
The association between serum uric acid (SUA) level and sexual dysfunction in patients with diabetes is not well characterized. Type 2 diabetes mellitus (T2DM) causes metabolic disorders, including abnormal serum uric acid (SUA) levels. In this study, we enrolled 205 male patients with T2DM and investigated the relationship between sex hormone levels and SUA. Patients were divided into four groups based on SUA quartiles. On the other hand, based on the total testosterone (TT) level, patients were divided into three groups; SUA and other laboratory indices were determined. Increase in SUA level was significantly associated with decreased levels of TT, luteinizing hormone, follicle-stimulating hormone, sex hormone-binding globulin, and increased levels of dehydroepiandrosterone, age, body mass index (BMI), waist circumference, glycated hemoglobin, serum creatinine, and HOMA-IR levels. SUA, waist circumference, BMI, and HOMA-IR showed a negative correlation with TT level, while age showed a positive correlation with TT level. SUA and body mass index were found to be risk factors for gonadal dysfunction. Therefore, we conclude that hypogonadism of male patients with T2DM is related to SUA level.
Background. Male hypogonadism is an endocrine disease characterized by low levels of serum testosterone and is closely related to the development of diabetes. The purpose of the present study was to observe the risk factors for hypogonadism in male patients with type 2 diabetes. Methods. A total of 213 patients with type 2 diabetes were enrolled and divided into a low total testosterone (TT) group (=75) and a normal TT group (=138). The patients' blood glucose, blood lipids, serum insulin, and sex hormones were measured. The correlations between the patients' metabolic index and sex hormone levels were analyzed. Results. Compared with the normal TT group, body mass index (BMI), fasting insulin (FINS), and HOMA insulin resistance index (HOMA-IR) levels were significantly higher, but the luteinizing hormone (LH) levels were significantly lower in the low TT group (p < 0.05). Correlation analyses found that TT was negatively correlated with BMI, waist circumference (WC), FINS, and HOMA-IR. TT was positively correlated with LH and follicle-stimulating hormone (FSH). Conclusions. Several risk factors of diabetes associated closely with hypogonadism. BMI, metabolic syndrome (MS), HOMA-IR, and LH are independent risk factors for hypogonadism in male patients with type 2 diabetes.
Association of HLA class II with multiple sclerosis (MS) has been widely studied in both Western and Oriental populations. However, such an association is not well documented in Chinese. The objective of this study was to examine the association between the susceptibility to conventional MS in Southern Chinese with HLA-DRB1,-DPB1 alleles and putative DRB1-DPB1 haplotypes. Genotyping of HLA-DRB1 and -DPB1 alleles was performed in 60 patients with conventional MS and 95 controls. Allele frequencies were compared between patients and controls to identify MS-associated alleles. Relative predisposing effect method was used to compare haplotype frequencies in patients and controls and to identify possible predisposing DRB1-DPB1 haplotypes, which were further examined for differences in haplotype carriage rates between the two groups. We found that the allele frequency of DRB1*1501 was not different between patients (18.3%) and controls (21.1%) (p = 0.837). In contrast, frequency of the DPB1*0501 allele was significantly higher in patients (90%) than in controls (67.4%) (odds ratio = 4.36, p = 0.0013, pcorr = 0.025). DRB1-DPB1 linkage haplotype in patients (8.33%) was significantly higher than in controls (0%) (p < 0.0001) and the carriage rate of this haplotype was significantly increased in patients (15%) as compared with controls (0%) (p = 0.00013, pcorr = 0.003). Combined, these results suggest that HLA-DRB1*1501 is not associated with susceptibility to conventional MS in Southern Chinese. Instead, both the DPB1*0501 allele and the DRB1*1602- DPB1*0501 haplotype are strong predisposing factors for conventional MS in this population. Our results establish that the HLA profiles of MS in Southern Chinese are distinct from other populations.
Background: Papillary thyroid cancer (PTC) is the most common form of well-differentiated endocrine malignancy. Distant metastases of PTC are rare and usually occur in the bones, lungs, and thoracic lymph nodes despite the common locoregional metastases to the lymph nodes of the neck. The metastasis of PTC to the pancreas is extremely rare. Here, we present a patient with PTC that had simultaneously metastasized to the pancreas, liver, and diaphragm. Case presentation: A 47-year-old male patient suffering from mild abdominal pain for 2 months was admitted to our hospital. The ultrasound (US) and computed tomography (CT) scan of the abdomen revealed a pancreatic space-occupying lesion and pancreatic duct dilatation, and the patient underwent exploratory laparotomy. Intraoperative examination identified a hard mass (approximately 4.0 cm × 3.0 cm) in the body and tail of the pancreas and a mass (1.5 cm in diameter) in the diaphragm. Three light masses were also noted on the surface of his liver. The patient underwent radical distal pancreatectomy, splenectomy, diaphragm, and liver mass resection. After surgery, the pathological report revealed that the masses resected from the pancreas, liver, and diaphragm were PTC metastases. Then, the patient had a thyroid US and an endoscopic US-guided fine needle aspiration biopsy of the thyroid mass. Pathology showed papillary cancer. Subsequently, the patient received a complete thyroidectomy, a cervical lymphadenectomy, bilateral parotidectomy, and bilateral submandibular gland resection. Conclusions: Aggressive surgeries, such as pancreaticoduodenectomy (PD), should be considered for selected patients with metastatic diseases from PTC to alleviate the symptoms and prolong their survival.
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